title: A study on the immunomodulation of polysaccharopeptide through the TLR4-TIRAP/MAL-MyD88 signaling pathway in PBMCs from breast cancer patients.
abstract: BACKGROUND
  Polysaccharopeptide (PSP), isolated from the Coriolus versicolor COV-1 strain, has been widely used as an immunoadjuvant for cancer immunotherapy.
  
  
  OBJECTIVE
  The present study was undertaken to examine the role of PSP on the TLR4-TIRAP/MAL-MyD88 signaling pathway in peripheral blood mononuclear cells (PBMCs) from breast cancer patients.
  
  
  METHODS
  For blockade of TLR4, cells were cultured with or without PSP and anti-TLR4 for 24 h, and then the mRNA and proteins (IL-12, IL-6, and TNF-α) levels in each group were detected by Q-PCR and ELISA. Meanwhile, Q-PCR and western blot analysis were used to detect the expression of TLR4-TIRAP/MAL-MyD88 pathway genes and proteins under the regulation of PSP.
  
  
  RESULTS
  As anticipated, the transcription and expression of genes (IL-12 and TNF-α) in the anti-TLR4 group were significantly downregulated compared with the control group, while genes (IL-12, IL-6 and TNF-α) in the PSP group were significantly upregulated. Moreover, the mRNA levels in the PSP+anti-TLR4 group were significantly upregulated compared with the anti-TLR4 group. The results of ELISA were as the same as Q-PCR. Genes, kinase phosphorylation levels and proteins in the TLR4 pathway were significantly upregulated by PSP.
  
  
  CONCLUSIONS
  Collectively, our study revealed that PSP has an immunoregulatory effect through regulation of the TLR4-TIRAP/MAL-MyD88 signaling pathway.
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.forename: Yi-Xi
authors.initials: YX
authors.lastname: Bao
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D055454:Trametes / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011509:Proteoglycans; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C093216:polysaccharide peptide